Methods and compositions for protecting and treating at least one muscarinic receptor from dysfunction not resulting from oxidative stress, toxic actions of metals or infectious agents by administering a pyrophosphate analog

Abstract

Methods and compositions for protecting and treating a muscarinic receptor in a subject in need thereof from dysfunction not resulting from oxidative stress, toxic actions of metals or metal ions, or infectious agents by administering a pyrophosphate analog.

1. A method for protecting and treating at least one muscarinic receptor from dysfunction resulting from free radical damage in a subject suffering from Alzheimer's disease, comprising administering an effective amount of pamidronate directly to the CNS of the subject and bypassing the blood-brain barrier by intranasally administering to the upper one-third of the subject's nasal cavity the effective amount of pamidronate 
       
         
           
           
               
               
           
         
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         protecting or treating the muscarinic receptors from the dysfunction resulting from free radical damage in the subjects in need thereof. 
       
     
     
       2. The method of  claim 1 , wherein the dysfunction further comprises damage to the ability of the muscarinic receptors to mediate the inhibitory and excitatory effects of the neurotransmitter acetylcholine wherein the at least one dysfunctional muscarinic receptor contributes to at least one disease or disorder. 
     
     
       3. The method of  claim 1 , wherein the subject is treated to improve memory and cognition contributed to by at least one dysfunctional muscarinic receptor. 
     
     
       4. The method of  claim 1 , wherein the dose of the at least one pyrophosphate analog administered to the subject is within the range of about 0.001 mg/kg to about 100 mg/kg. 
     
     
       5. The method of  claim 1 , wherein the dose of pamidronate administered to the subject is within the range of about 0.01 mg/kg to about 10 mg/kg. 
     
     
       6. The method of  claim 1 , wherein the dose of pamidronate administered to the subject is within the range of about 0.1 mg/kg to about 1 mg/kg. 
     
     
       7. The method of  claim 2 , further comprising protecting and treating the muscarinic receptors that mediate the effects of acetylcholine in the brain. 
     
     
       8. The method of  claim 1  wherein the free radical damage results from oxidative stress. 
     
     
       9. The method of  claim 1  wherein the free radical damage results from metal toxicity.